Hepatic inhibitors expression profiling of venom-challenged Sinonatrix annularis and antidotal activities - 15/11/22

Abstract |
Snake venom is considered a “toxin arsenal”, and it often induces a series of clinical and pathophysiological symptoms in snakebite victims. Interestingly, toxin inhibitors are commonly found in the serum of snakes and their predators. Sinonatrix annularis is a type of non-venomous snake that was reported to contain an “inhibitor cocktail”, including phospholipase A2 inhibitors (PLIs), metalloproteinase inhibitors (SVMPIs), and small serum protein (SSP). However, the sequences and activities of these components remain obscure. In this study, we performed envenomation challenges on S. annularis using venoms from Deinagkistrodon acutus, Agkistrodon halys and Naja atra. In brief, the maximum injected amount of venom was 360 mg/kg for D. acutus, 72 mg/kg for A. halys, and 18 mg/kg for N. atra. The mRNA expression of the inhibitors PLIα, PLIβ, PLIγ, SVMPI, serpin A1, and SSP showed a dose-dependent effect on envenomation. Liver homogenate from S. annularis (LH) was prepared and used to evaluate its inhibitory effect on snake venoms. As a result, LH showed significant neutralization of venom PLA2, mitigated hemorrhage, venom-induced muscle damage, and system toxicity. In the presence of LH, envenomated mice exhibited attenuated inflammation, apoptosis, oxidative damage, and mitigated changes in serum biochemical markers caused by venom. The study reveals the secret of “natural immunity” in snakes, namely, the “antivenom”, which consists of an inhibitor proteome or cocktail.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | S. annularis showed good tolerance to different snake venoms due to their intrinsic inhibitor cocktail. |
• | The inhibitors were upregulated in a dose-dependent manner in response to venom exposure. |
• | The liver homogenate of S. annularis attenuated envenoming symptoms in victim mice. |
Abbreviations : DA, AH, NA, PLA2, SVMP, CLEC, SVSP, PLI, CK, LDH, AST, ALT, HSF, PSP94, SSP, AAT, CAT, GR, MDA, SEM, TBARS, WHO, Bcl-2, Bax, GAPDH
Keywords : Sinonatrix annularis, RNA-seq library, Snake venom, Inhibitors of toxins, Gene expression
Plan
Vol 156
Article 113900- décembre 2022 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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